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Data Supporting The Roles Of Bap1, Sting, And Ifn-Β In Isgf3 Activation In Ccrcc, Lauren E Langbein, Eleonora Sementino, Zhijiu Zhong, Wei Jiang, Li Li, Joseph R Testa, Haifeng Yang 2022 Thomas Jefferson University

Data Supporting The Roles Of Bap1, Sting, And Ifn-Β In Isgf3 Activation In Ccrcc, Lauren E Langbein, Eleonora Sementino, Zhijiu Zhong, Wei Jiang, Li Li, Joseph R Testa, Haifeng Yang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The data presented in this article are companion materials to our manuscript titled "BAP1 maintains HIF-dependent interferon beta induction to suppress tumor growth in clear cell renal cell carcinoma" (Langbein et al., 2022), where we investigated the downstream effects of BAP1 (BRCA1-associated protein 1) expression in clear cell renal cell carcinoma (ccRCC) cell lines and mouse xenograft models. In the manuscript, we showed that BAP1 upregulates STING (stimulator of interferon genes) expression and activity in ccRCC cells, leading to IFN-β transcription and activation of interferon stimulated gene factor 3 (ISGF3), the transcription factor that mediates the effects of type I …


Bcl11b And Atoh8 Coordinate Cellular Plasticity For Reprogramming And Transformation, Mo-Fan Huang, Rachel Shoemaker, Dung-Fang Lee 2022 The Texas Medical Center Library

Bcl11b And Atoh8 Coordinate Cellular Plasticity For Reprogramming And Transformation, Mo-Fan Huang, Rachel Shoemaker, Dung-Fang Lee

Journal Articles

By dissecting and comparing the transcriptional trajectories and epigenomic traits of reprogramming and transforming cells at the single-cell resolution, Huyghe et al discovered Bcl11b and Atoh8, two key transcription factors controlling cell plasticity during pluripotent reprogramming and oncogenic transformation.


Risk-Factor Induced Changes In The Breast Microenvironment Facilitate Inflammatory Breast Cancer Progression And Lymphovascular Invasion, Wintana Balema, Wintana Balema 2022 MD Anderson Cancer Center

Risk-Factor Induced Changes In The Breast Microenvironment Facilitate Inflammatory Breast Cancer Progression And Lymphovascular Invasion, Wintana Balema, Wintana Balema

Dissertations & Theses (Open Access)

Inflammatory breast cancer (IBC) is a rapidly progressing, rare and highly lethal form of breast cancer. IBC is a clinical diagnosis, requiring >1/3 involvement on the affected breast and/or skin by erythema, and disease onset of < 6 months. The clinical symptoms of IBC vary in severity and presentation, these include redness, warmth, skin thickening and bruised or pink/purple discoloration appearance and skin changes such as peau d’orange. These skin symptoms are not attributed to inflammation, rather IBC is characterized by florid lymphovascular tumor emboli clogging dermal lymphatics. This leads to “classic” symptoms of breast swelling and skin edema or discoloration. To date, unique genomic drivers which differentiate IBC from non-IBC invasive breast cancers have not been identified highlighting a role for the microenvironment. Several epidemiological studies have unveiled subtype-specific risk factors associated with IBC that are known to alter the microenvironment. Obesity is an established risk factor for all subtypes of IBC. Never-breastfeeding increases risk for developing the most aggressive, triple-negative IBC. Further, never breastfeeding is associated with later clinical stage and worse outcomes. We worked to model these overlapping risk factors to understand microenvironment changes that may lead to the lymphatic change’s indicative of IBC.

First, we investigated the association of a “classic” triad of clinical IBC signs with overall survival among patients to demonstrate the most overt clinical findings of lymphatic involvement were impacting prognosis. We evaluated a triad of IBC signs, including swollen involved breast, nipple change, and diffuse skin change, using breast medical photographs from patients enrolled on a prospective IBC registry. We reported that the …


Altered Expression Of Glycobiology-Related Genes In Parkinson’S Disease Brain, Jay S Schneider, Garima Singh 2022 Thomas Jefferson University

Altered Expression Of Glycobiology-Related Genes In Parkinson’S Disease Brain, Jay S Schneider, Garima Singh

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The precise mechanisms initiating and perpetuating the cellular degeneration in Parkinson's disease (PD) remain unclear. There is decreased expression of the main brain gangliosides, and GM1 ganglioside in particular, in the PD brain along with decreased expression of the genes coding for the glycosyltranferase and the sialyltransferase responsible for the synthesis of these brain gangliosides. However, potentially important pathogenic mechanisms contributing to the neurodegeneration in PD may also include altered levels of expression of genes involved in glycosylation, sialylation and sphingolipid synthesis and metabolism. Although various studies have described pathological lipid and glycolipid changes in PD brain, there have been …


Genome-Scale Metabolic Modeling Reveals Sequential Dysregulation Of Glutathione Metabolism In Livers From Patients With Alcoholic Hepatitis, Alexandra Manchel, Radhakrishnan Mahadevan, Ramon Bataller, Jan B. Hoek, Rajanikanth Vadigepalli 2022 Thomas Jefferson University

Genome-Scale Metabolic Modeling Reveals Sequential Dysregulation Of Glutathione Metabolism In Livers From Patients With Alcoholic Hepatitis, Alexandra Manchel, Radhakrishnan Mahadevan, Ramon Bataller, Jan B. Hoek, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Alcoholic hepatitis (AH) is the most severe form of alcoholic liver disease for which there is no efficacious treatment aiding most patients. AH manifests differently in individuals, with some patients showing debilitating symptoms more so than others. Previous studies showed significant metabolic dysregulation associated with AH. Therefore, we sought to analyze how the activity of metabolic pathways differed in the liver of patients with varying degrees of AH severity. We utilized a genome-scale metabolic modeling approach that allowed for integration of a generic human cellular metabolic model with specific RNA-seq data corresponding to healthy and multiple liver disease states to …


Corneal Edema Associated With Degenerating Soemmering Ring Cataract: Clinical-Pathologic Correlation, Jordan P Safran, Nathan Nataneli, Jayesh Vazirani, Ralph C. Eagle Jr, Tatyana Milman 2022 Thomas Jefferson University

Corneal Edema Associated With Degenerating Soemmering Ring Cataract: Clinical-Pathologic Correlation, Jordan P Safran, Nathan Nataneli, Jayesh Vazirani, Ralph C. Eagle Jr, Tatyana Milman

Wills Eye Hospital Papers

Purpose: To report three patients with an uncommon delayed complication of cataract extraction: corneal edema following dispersion of calcific lens particles from a degenerating Soemmering ring cataract.

Observations: We report three patients, 75-92 years old, presenting with corneal edema and dispersed, degenerated calcific lens material in the anterior chamber and vitreous 20-30 years after cataract surgery. In all patients, calcific particles studded the posterior surface of the cornea in a gravity-dependent distribution without apparent inflammation and were associated with localized corneal edema. In one patient, calcific particles were also associated with secondary open angle glaucoma. Deposits originated from the calcified …


Capture At The Er-Mitochondrial Contacts Licenses Ip, Máté Katona, Ádám Bartók, Zuzana Nichtova, György Csordás, Elena Berezhnaya, David Weaver, Arijita Ghosh, Péter Várnai, David I. Yule, György Hajnóczky 2022 Thomas Jefferson University

Capture At The Er-Mitochondrial Contacts Licenses Ip, Máté Katona, Ádám Bartók, Zuzana Nichtova, György Csordás, Elena Berezhnaya, David Weaver, Arijita Ghosh, Péter Várnai, David I. Yule, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Endoplasmic reticulum-mitochondria contacts (ERMCs) are restructured in response to changes in cell state. While this restructuring has been implicated as a cause or consequence of pathology in numerous systems, the underlying molecular dynamics are poorly understood. Here, we show means to visualize the capture of motile IP3 receptors (IP3Rs) at ERMCs and document the immediate consequences for calcium signaling and metabolism. IP3Rs are of particular interest because their presence provides a scaffold for ERMCs that mediate local calcium signaling, and their function outside of ERMCs depends on their motility. Unexpectedly, in a cell model with little ERMC Ca2+ coupling, IP3Rs …


Pi3k Isoform-Specific Regulation Of Leader And Follower Cell Function For Collective Migration And Proliferation In Response To Injury, Morgan D Basta, A. Menko, Janice L Walker 2022 Thomas Jefferson University

Pi3k Isoform-Specific Regulation Of Leader And Follower Cell Function For Collective Migration And Proliferation In Response To Injury, Morgan D Basta, A. Menko, Janice L Walker

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

To ensure proper wound healing it is important to elucidate the signaling cues that coordinate leader and follower cell behavior to promote collective migration and proliferation for wound healing in response to injury. Using an ex vivo post-cataract surgery wound healing model we investigated the role of class I phosphatidylinositol-3-kinase (PI3K) isoforms in this process. Our findings revealed a specific role for p110α signaling independent of Akt for promoting the collective migration and proliferation of the epithelium for wound closure. In addition, we found an important role for p110α signaling in orchestrating proper polarized cytoskeletal organization within both leader and …


Editorial: Epigenetics And Molecular Genetics Of Rare Tumors, Mauro Tognon, George A. Calin, Luis Del Valle 2022 University of Ferrara, Ferrara, Italy

Editorial: Epigenetics And Molecular Genetics Of Rare Tumors, Mauro Tognon, George A. Calin, Luis Del Valle

School of Medicine Faculty Publications

No abstract provided.


Bap1 Maintains Hif-Dependent Interferon Beta Induction To Suppress Tumor Growth In Clear Cell Renal Cell Carcinoma., Lauren Langbein, Rayan El Hajjar, Shen He, Eleonora Sementino, Zhijiu Zhong, Wei Jiang, Benjamin E Leiby, Li Li, Robert G Uzzo, Joseph R Testa, Haifeng Yang 2022 Thomas Jefferson University

Bap1 Maintains Hif-Dependent Interferon Beta Induction To Suppress Tumor Growth In Clear Cell Renal Cell Carcinoma., Lauren Langbein, Rayan El Hajjar, Shen He, Eleonora Sementino, Zhijiu Zhong, Wei Jiang, Benjamin E Leiby, Li Li, Robert G Uzzo, Joseph R Testa, Haifeng Yang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BRCA1-associated protein 1 (BAP1) is a deubiquitinase that is mutated in 10-15% of clear cell renal cell carcinomas (ccRCC). Despite the association between BAP1 loss and poor clinical outcome, the critical tumor suppressor function(s) of BAP1 in ccRCC remains unclear. Previously, we found that hypoxia-inducible factor 2α (HIF2α) and BAP1 activate interferon-stimulated gene factor 3 (ISGF3), a transcription factor activated by type I interferons and a tumor suppressor in ccRCC xenograft models. Here, we aimed to determine the mechanism(s) through which HIF and BAP1 regulate ISGF3. We found that in ccRCC cells, loss of the von Hippel-Lindau tumor suppressor (VHL) …


Motoneuron Excitability Dysfunction In Als: Pseudo-Mystery Or Authentic Conundrum?, Sherif M. Elbasiouny 2022 Wright State University - Main Campus

Motoneuron Excitability Dysfunction In Als: Pseudo-Mystery Or Authentic Conundrum?, Sherif M. Elbasiouny

Neuroscience, Cell Biology & Physiology Faculty Publications

In amyotrophic lateral sclerosis (ALS), abnormalities in motoneuronal excitability are seen in early pathogenesis and throughout disease progression. Fully understanding motoneuron excitability dysfunction may lead to more effective treatments. Yet decades of research have not produced consensus on the nature, role or underlying mechanisms of motoneuron excitability dysfunction in ALS. For example, contrary to Ca excitotoxicity theory, predictions of motoneuronal hyper-excitability, normal and hypo-excitability have also been seen at various disease stages and in multiple ALS lines. Accordingly, motoneuron excitability dysfunction in ALS is a disputed topic in the field. Specifically, the form (hyper, hypo or unchanged) and what role …


Activity Of Prefrontal Cortex Subpopulations During Operant Alcohol Selfadministration, Grant Collins, H. Mejia Gomez, Faith Maxwell, Jessica M. Patel, Michael Salling 2022 LSU Health Sciences Center- New Orleans

Activity Of Prefrontal Cortex Subpopulations During Operant Alcohol Selfadministration, Grant Collins, H. Mejia Gomez, Faith Maxwell, Jessica M. Patel, Michael Salling

Medical Student Research Poster Symposium

The National Institute of Alcohol Abuse and Alcoholism states, ‘according to the 2019 [National Survey on Drug Use and Health], 14.5 million (nearly 15 million) people ages 12 and older1 (5.3 percent of this age group2 ) had [alcohol use disorder (AUD)].’ The DSM-5 criteria for AUD includes compulsive drinking behavior.3 The prefrontal cortex (PFC) has roles in decisionmaking, response inhibition, and drug seeking and likely plays a role in compulsive alcohol drinking. However, the specific circuitry involved is unknown. There are two PFC circuits implicated in response inhibition or ‘stop’ behavior: PFC projections to the dorsomedial striatum (DMS) and …


Relationship Between Depression And Cognitive Impairment In Patients With Multiple Sclerosis, Alexandra Nguyen, Yazmeen Allen, Natalie Thayer, Shannin Moody, Deidre Devier 2022 LSU Health Sciences Center- New Orleans

Relationship Between Depression And Cognitive Impairment In Patients With Multiple Sclerosis, Alexandra Nguyen, Yazmeen Allen, Natalie Thayer, Shannin Moody, Deidre Devier

Medical Student Research Poster Symposium

Background: Multiple Sclerosis (MS) is an autoimmune, neurodegenerative disease characterized by chronic inflammation and demyelination of the brain and spinal cord. This deterioration of the central nervous system leads to a wide range of motor, cognitive, and neuropsychiatric symptoms. Each patient varies in symptom profile and disease course. However, cognitive impairment has been found in roughly half of all people with MS regardless of MS subtype. This may present as deficits in attention, information processing speed, executive function, and visuospatial perception. This impairment may interfere with basic and instrumental activities of daily living, vocational status, and social functioning; all of …


Detailing The Effects Of Cbd On Parp And Survivin Expression In Ewing Sarcoma, Tyler Carter 2022 Jacksonville State University

Detailing The Effects Of Cbd On Parp And Survivin Expression In Ewing Sarcoma, Tyler Carter

Theses

Ewing sarcoma (ES) is an aggressive pediatric bone cancer with low five-year survival rates, particularly with recurrent disease because ES often becomes resistant to chemotherapy in these recurrences. Cannabidiol (CBD) has been identified as a potentially promising therapeutic for patients with ES. In other cancer types, CBD has demonstrated effects on two major proteins that contribute to chemotherapy resistance. The first, Poly (ADP-ribose) Polymerase I (PARP1), is a DNA damage repair enzyme that is overexpressed in recurrent ES. Though chemotherapy induces DNA damage in these cancer cells, the high levels of PARP1 facilitate repair of the DNA, allowing the mutated …


Artificial Gravity Partially Protects Space-Induced Neurological Deficits In Drosophila Melanogaster, Amber M. Paul, Siddhita D. Mhatre, Janani Iyer, Juli Petereit, Roberta M. Dolling-Boreham 2022 Embry-Riddle Aeronautical University

Artificial Gravity Partially Protects Space-Induced Neurological Deficits In Drosophila Melanogaster, Amber M. Paul, Siddhita D. Mhatre, Janani Iyer, Juli Petereit, Roberta M. Dolling-Boreham

Publications

Spaceflight poses risks to the central nervous system (CNS), and understanding neurological responses is important for future missions. We report CNS changes in Drosophila aboard the International Space Station in response to spaceflight microgravity (SFmg) and artificially simulated Earth gravity (SF1g) via inflight centrifugation as a countermeasure. While inflight behavioral analyses of SFmg exhibit increased activity, postflight analysis displays significant climbing defects, highlighting the sensitivity of behavior to altered gravity. Multiomics analysis shows alterations in metabolic, oxidative stress and synaptic transmission pathways in both SFmg and SF1g; however, neurological changes immediately postflight, including neuronal loss, glial cell count alterations, oxidative …


Non-Invasive Transcutaneous Spinal Dc Stimulation As A Neurorehabilitation Als Therapy In Awake G93a Mice: The First Step To Clinical Translation, Morgan M. Highlander, Sherif M. Elbasiouny 2022 Wright State University

Non-Invasive Transcutaneous Spinal Dc Stimulation As A Neurorehabilitation Als Therapy In Awake G93a Mice: The First Step To Clinical Translation, Morgan M. Highlander, Sherif M. Elbasiouny

Neuroscience, Cell Biology & Physiology Faculty Publications

Spinal direct current stimulation (sDCS) modulates motoneuron (MN) excitability beyond the stimulation period, making it a potential neurorehabilitation therapy for amyotrophic lateral sclerosis (ALS), a MN degenerative disease in which MN excitability dysfunction plays a critical and complex role. Recent evidence confirms induced changes in MN excitability via measured MN electrophysiological properties in the SOD1 ALS mouse during and following invasive subcutaneous sDCS (ssDCS). The first aim of our pilot study was to determine the clinical potential of these excitability changes at symptom onset (P90-P105) in ALS via a novel non-invasive transcutaneous sDCS (tsDCS) treatment paradigm on un-anesthetized SOD1-G93A mice. …


Suppression Of Store-Operated Calcium Entry Channels And Cytokine Release By Cannabinoids, J. Ashot Kozak 2022 Wright State University - Main Campus

Suppression Of Store-Operated Calcium Entry Channels And Cytokine Release By Cannabinoids, J. Ashot Kozak

Neuroscience, Cell Biology & Physiology Faculty Publications

No abstract provided.


Unreliable Automated Complete Blood Count Results: Causes, Recognition, And Resolution, Gene Gulati, Guldeep Uppal, Jerald Z. Gong 2022 Thomas Jefferson University

Unreliable Automated Complete Blood Count Results: Causes, Recognition, And Resolution, Gene Gulati, Guldeep Uppal, Jerald Z. Gong

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Automated hematology analyzers generate accurate complete blood counts (CBC) results on nearly all specimens. However, every laboratory encounters, at times, some specimens that yield no or inaccurate result(s) for one or more CBC parameters even when the analyzer is functioning properly and the manufacturer's instructions are followed to the letter. Inaccurate results, which may adversely affect patient care, are clinically unreliable and require the attention of laboratory professionals. Laboratory professionals must recognize unreliable results, determine the possible cause(s), and be acquainted with the ways to obtain reliable results on such specimens. We present a concise overview of the known causes …


Role Of Decorin At The Fetal-Maternal Interface, Chidambra D. Halari 2022 The University of Western Ontario

Role Of Decorin At The Fetal-Maternal Interface, Chidambra D. Halari

Electronic Thesis and Dissertation Repository

The human placenta is an invasive tumor-like structure, this invasion being physiological. A subset of placental trophoblast called extra-villous trophoblast invades the uterine decidua and remodels uterine arteries into low-resistance, high-flow tubes to permit adequate flow of maternal blood to nourish the fetus. A poor extra-villous trophoblast invasion and uterine arterial remodeling can lead to fetal growth restriction and a serious pregnancy-associated maternal disease preeclampsia. Decorin, a leucine-rich proteoglycan produced by uterine decidual cells restrains multiple trophoblast functions: self-renewal and differentiation of trophoblast stem cells, migration, invasion, proliferation and endovascular differentiation. Additionally, decidual overproduction of decorin was associated with preeclampsia, …


Hashimoto’S Thyroiditis Minimizes Lymph Node Metastasis In Braf Mutant Papillary Thyroid Carcinomas, Peter P. Issa, Mahmoud Omar, Yusef Buti, Chad P. Issa, Bert Chabot, Christopher J. Carnabatu, Ruhul Munshi, Mohammad Hussein, Mohamed Aboueisha, Mohamed Shama, Ralph L. Corsetti, Eman Toraih, Emad Kandil 2022 LSU Health Sciences Center - New Orleans

Hashimoto’S Thyroiditis Minimizes Lymph Node Metastasis In Braf Mutant Papillary Thyroid Carcinomas, Peter P. Issa, Mahmoud Omar, Yusef Buti, Chad P. Issa, Bert Chabot, Christopher J. Carnabatu, Ruhul Munshi, Mohammad Hussein, Mohamed Aboueisha, Mohamed Shama, Ralph L. Corsetti, Eman Toraih, Emad Kandil

School of Medicine Faculty Publications

Hashimoto’s thyroiditis (HT) (autoimmune thyroiditis) is a clinicopathological entity associated with chronic lymphocytic infiltration resulting in hypothyroidism. HT is a double-edged sword that increases the risk of papillary thyroid cancer (PTC), yet it serves as a protective factor for PTC progression. BRAF mutation in PTCs is associated with rapid cell growth, aggressive tumor characteristics, and higher mortality rates. Here, we aimed to analyze the influence of HT in patients with PTCs and its effect on lymph node metastasis (LNM) in BRAF mutant tumors. Adults diagnosed with PTC between 2008 and January 2021 were retrospectively included. A total of 427 patients, …


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